Predictors of treatment failures of plasmodium falciparum malaria in Vietnam: a 4-year single‐centre retrospective study

Abstract Background Drug-resistant falciparum malaria is an increasing public health burden. This study examined the magnitude of Plasmodium falciparum infection and the patterns and predictors of treatment failure in Vietnam. Methods Medical records of all 443 patients with malaria infection admitted to the Hospital for Tropical Diseases between January 2015 and December 2018 were used to extract information on demographics, risk factors, symptoms, laboratory tests, treatment, and outcome. Results More than half (59.8%, 265/443, CI 55.1–64.4%) of patients acquired Plasmodium falciparum infection of whom 21.9% (58/265, CI 17.1–27.4%) had severe malaria, while 7.2% (19/265, CI 4.6–10.9%) and 19.2% (51/265, CI 14.7–24.5%) developed early treatment failure (ETF) and late treatment failure (LTF) respectively. Among 58 patients with severe malaria, 14 (24.1%) acquired infection in regions where artemisinin resistance has been documented including Binh Phuoc (11 patients), Dak Nong (2 patients) and Gia Lai (1 patient). Under treatment with intravenous artesunate, the median (IQR) parasite half-life of 11 patients coming from Binh Phuoc was 3 h (2.3 to 8.3 h), two patients coming from Dak Nong was 2.8 and 5.7 h, and a patient coming from Gia Lai was 6.5 h. Most patients (98.5%, 261/265) recovered completely. Four patients with severe malaria died. Severe malaria was statistically associated with receiving treatment at previous hospitals (P < 0.001), hepatomegaly (P < 0.001) and number of inpatient days (P < 0.001). Having severe malaria was a predictor of ETF (AOR 6.96, CI 2.55–19.02, P < 0.001). No predictor of LTF was identified. Conclusions Plasmodium falciparum remains the prevalent malaria parasite. Despite low mortality rate, severe malaria is not rare and is a significant predictor of ETF. To reduce the risk for ETF, studies are needed to examine the effectiveness of combination therapy including parenteral artesunate and a parenteral partner drug for severe malaria. The study alerts the possibility of drug-resistant malaria in Africa and other areas in Vietnam, which are known as non-endemic areas of anti-malarial drug resistance. A more comprehensive study using molecular technique in these regions is required to completely understand the magnitude of drug-resistant malaria and to design appropriate control strategies.

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Predictors of treatment failures of Plasmodium falciparum malaria in Vietnam: a 4-year single-center retrospective study

10.21203/rs.3.rs-126234/v1 ◽

2020 ◽

Author(s):

Minh Cuong Duong ◽

Oanh Kieu Nguyet Pham ◽

Phong Thanh Nguyen ◽

Chau Van Vinh Nguyen ◽

Phu Hoan Nguyen

Keyword(s):

Plasmodium Falciparum ◽

Treatment Failure ◽

Severe Malaria ◽

Falciparum Malaria ◽

Control Strategies ◽

Plasmodium Falciparum Malaria ◽

Molecular Technique ◽

Drug Resistant ◽

Public Health Burden ◽

Central Highland

Abstract BackgroundDrug-resistant falciparum malaria is an increasing public health burden. We examined the magnitude of Plasmodium falciparum infection and the patterns and predictors of treatment failure in Vietnam. MethodsMedical records of all 443 patients with malaria infection admitted to the Hospital for Tropical Diseases between January 2015 and December 2018 were used to extract information on demographics, risk factors, symptoms, laboratory tests, treatment, and outcomes. ResultsMore than half (59.8%, CI 55.1%-64.4%) of patient acquired P. falciparum infection of whom 21.9% (CI 17.1%-27.4%) had severe malaria, while 7.2% (CI 4.6%-10.9%) and 19.2% (CI 14.7%-24.5%) developed early treatment failure (ETF) and late treatment failure (LTF) respectively. ETF was 4.7% among patients referred from Binh Phuoc province and Central Highland, 12.9% from other areas in Vietnam, and 6.9% from Africa. LTF was 16.2% among patients from Binh Phuoc province and Central Highland, 22.6% from other areas in Vietnam, and 27.6% from Africa. Most patients (98.5%) recovered completely. Having severe malaria was a predictor of ETF (AOR 6.96, CI 2.55-19.02, P < 0.001). No predictor of LTF was identified.ConclusionP. falciparum remains the prevalent malaria parasite. Despite low mortality rate, severe malaria is not rare and is a significant predictor of ETF. To reduce the risk for ETF, studies are needed to examine the effectiveness of combination therapy including parenteral artesunate and a parenteral partner drug for severe malaria. The study alerts the possibility of drug-resistant malaria in Africa and other areas in Vietnam which are known as nonendemic areas of antimalarial drug resistance. A more comprehensive study using molecular technique in these regions is required to completely understand the magnitude of drug-resistant malaria and to design appropriate control strategies.

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Spread of multidrug-resistant Plasmodium falciparum malaria and predictors of treatment failures in Vietnam

10.21203/rs.2.18720/v1 ◽

2019 ◽

Author(s):

Minh Cuong Duong ◽

Oanh Kieu Nguyet Pham ◽

Phong Thanh Nguyen ◽

Van Vinh Chau Nguyen ◽

Phu Hoan Nguyen

Keyword(s):

Plasmodium Falciparum ◽

Treatment Failure ◽

Severe Malaria ◽

Falciparum Malaria ◽

Early Treatment ◽

Molecular Technique ◽

Drug Resistant ◽

Early Treatment Failure ◽

Central Highland ◽

Late Treatment

Abstract Background Drug-resistant falciparum malaria is an increasing public health burden. We examined the magnitude of Plasmodium falciparum infection and the patterns and predictors of treatment failure in Vietnam. Methods Medical records of all 443 patients with malaria infection admitted to the Hospital for Tropical Diseases between January 2015 and December 2018 were used to extract information on demographics, risk factors, symptoms, laboratory tests, treatment, and outcome. Results More than half (59.8%, 95%CI 55.1%-64.4%) of patient acquired P. falciparum infection of whom 21.9% (95%CI 17.1%-27.4%) had severe malaria, while 10.2% (95%CI 6.8%-14.5%) and 19.2% (95%CI 14.7%-24.5%) developed early treatment failure (ETF) and late treatment failure (LTF) respectively. ETF was 6.8% among patients referred from Binh Phuoc province and Central Highland, 11.3% from other areas in Vietnam, and 6.9% from Africa. LTF was 16.2% among patients from Binh Phuoc province and Central Highland, 22.6% from other areas in Vietnam, and 27.6% from Africa. Most patients (98.5%) recovered completely. Having severe malaria was a predictor of ETF (AOR 4.42, 95%CI 1.85-10.61, P = 0.001). No predictor of LTF was identified.Conclusion P. falciparum remains the prevalent malaria parasite. Despite low mortality rate, severe malaria is not rare and is a significant predictor of ETF. Parenteral artesunate and an oral partner drug should be concurrently used for severe malaria to reduce the risk for ETF. The study alerts the possibility of drug-resistant malaria in Africa and other areas in Vietnam which are known as nonendemic areas of antimalarial drug resistance. A more comprehensive study using molecular technique in these regions is required to completely understand the magnitude of drug-resistant malaria and to design appropriate control strategies. Key words: Plasmodium falciparum; severe malaria; early treatment failure; late treatment failure; Vietnam

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pfk13-Independent Treatment Failure in Four Imported Cases of Plasmodium falciparum Malaria Treated with Artemether-Lumefantrine in the United Kingdom

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02382-16 ◽

2017 ◽

Vol 61 (3) ◽

Cited By ~ 58

Author(s):

Colin J. Sutherland ◽

Paul Lansdell ◽

Mandy Sanders ◽

Julian Muwanguzi ◽

Donelly A. van Schalkwyk ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Treatment Failure ◽

Falciparum Malaria ◽

Artemisinin Resistance ◽

Plasmodium Falciparum Malaria ◽

African Origin ◽

Case Histories ◽

Content Type ◽

The United Kingdom ◽

Imported Cases

ABSTRACT We present case histories of four patients treated with artemether-lumefantrine for falciparum malaria in UK hospitals in 2015 to 2016. Each subsequently presented with recurrent symptoms and Plasmodium falciparum parasitemia within 6 weeks of treatment with no intervening travel to countries where malaria is endemic. Parasite isolates, all of African origin, harbored variants at some candidate resistance loci. No evidence of pfk13-mediated artemisinin resistance was found. Vigilance for signs of unsatisfactory antimalarial efficacy among imported cases of malaria is recommended.

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Faculty of 1000 evaluation for Endoglin in African children with Plasmodium falciparum malaria: a novel player in severe malaria pathogenesis?

F1000 - Post-publication peer review of the biomedical literature ◽

10.3410/f.1691966.1198069 ◽

2010 ◽

Author(s):

Charles Newton ◽

Samson Gwer

Keyword(s):

Plasmodium Falciparum ◽

Severe Malaria ◽

Falciparum Malaria ◽

Plasmodium Falciparum Malaria ◽

African Children

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A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria

Nature ◽

10.1038/nature14412 ◽

2015 ◽

Vol 520 (7549) ◽

pp. 683-687 ◽

Cited By ~ 320

Author(s):

Alassane Mbengue ◽

Souvik Bhattacharjee ◽

Trupti Pandharkar ◽

Haining Liu ◽

Guillermina Estiu ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Molecular Mechanism ◽

Falciparum Malaria ◽

Artemisinin Resistance ◽

Plasmodium Falciparum Malaria

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Efficacy of dihydroartemisinin/piperaquine and artesunate monotherapy for the treatment of uncomplicated Plasmodium falciparum malaria in Central Vietnam

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkaa172 ◽

2020 ◽

Author(s):

Eduard Rovira-Vallbona ◽

Nguyen Van Hong ◽

Johanna H Kattenberg ◽

Ro Mah Huan ◽

Nguyen Thi Thu Hien ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Falciparum Malaria ◽

Ex Vivo ◽

Survival Rates ◽

Artemisinin Resistance ◽

Plasmodium Falciparum Malaria ◽

Parasite Clearance ◽

Resistance Mutations ◽

Malaria Burden ◽

Central Vietnam

Abstract Background Artemisinin-based combination therapies (ACTs) have significantly contributed to reduce Plasmodium falciparum malaria burden in Vietnam, but their efficacy is challenged by treatment failure of dihydroartemisinin/piperaquine ACT in Southern provinces. Objectives To assess the efficacy of dihydroartemisinin/piperaquine for uncomplicated P. falciparum malaria in Gia Lai, Central Vietnam, and determine parasite resistance to artemisinin (ClinicalTrials.gov identifier NCT02604966). Methods Sixty patients received either dihydroartemisinin/piperaquine (4 mg/kg/day, 3 days; n = 33) or artesunate monotherapy (4 mg/kg/day, 3 days; n = 27) followed by dihydroartemisinin/piperaquine (AS + DHA/PPQ). Clinical phenotypes were determined during a 42 day follow-up and analysed together with ex vivo susceptibility to antimalarials and molecular markers of drug resistance. Results Day 3 positivity rate was significantly higher in the AS + DHA/PPQ arm compared with dihydroartemisinin/piperaquine (70.4% versus 39.4%, P = 0.016). Parasite clearance time was 95.2 h (AS + DHA/PPQ) versus 71.9 h (dihydroartemisinin/piperaquine, P = 0.063) and parasite clearance half-life was 7.4 h (AS + DHA/PPQ) versus 7.0 h (dihydroartemisinin/piperaquine, P = 0.140). Adequate clinical and parasitological response at Day 42 was 100% in both arms. By RT–qPCR, 36% (19/53) patients remained positive until Day 7. No recurrences were detected. kelch13 artemisinin resistance mutations were found in 87% (39/45) of isolates and 50% (20/40) were KEL1/C580Y. The piperaquine resistance marker plasmepsin-2 was duplicated in 10.4% (5/48). Isolates from Day 3-positive patients (n = 18) had higher ex vivo survival rates to artemisinin compounds (P < 0.048) and prevalence of kelch13 mutations (P = 0.005) than Day 3-negative patients (n = 5). The WHO definition of artemisinin resistance was fulfilled in 60% (24/40) of cases. Conclusions Although dihydroartemisinin/piperaquine remained effective to treat P. falciparum, the high Day 3 positivity rate and prevalence of KEL1 strains calls for continuous monitoring of dihydroartemisinin/piperaquine efficacy in Central Vietnam.

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